Antiphospholipid syndrome (Hughes syndrome) is characterized by the presence of arterial or venou... more Antiphospholipid syndrome (Hughes syndrome) is characterized by the presence of arterial or venous thrombosis or recurrent miscarriages in a patient with positive laboratory tests for antiphospholipid antibodies (anticardiolipin antibodies and/or lupus anticoagulant and/or anti-beta(2) glycoprotein I). Despite the strong association between antiphospholipid antibodies, and thrombosis and obstetric morbidity, their pathogenic role in the development of these clinical features has not been fully elucidated. At present, patients with thrombosis are treated with long-term oral anticoagulation as standard. The approach for women with obstetric manifestations is based on the use of aspirin plus heparin. However, the knowledge of new pathogenic mechanisms might identify novel therapeutic targets and, therefore, may improve the management of these patients.
To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and ... more To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outc...
The catastrophic variant of the antiphospholipid syndrome (APS) is the most severe and acute form... more The catastrophic variant of the antiphospholipid syndrome (APS) is the most severe and acute form of APS with multiorgan involvement. Patients with this condition have the following features in common: a) clinical evidence of multiple organ involvement developed over a very short time period; b) histopathological evidence of multiple small vessel occlusions, and c) laboratory confirmation of the presence of antiphospholipid antibodies, usually in high titer. The two key pathobiologic mechanisms that cause the clinical manifestations of catastrophic APS are the development of thrombosis and the systemic inflammatory response syndrome. A precipitating factor is reported in more than half of patients. A combination of anticoagulants, corticosteroids, intravenous immunoglobulins and/or plasma exchanges are the treatment modalities advocated for all patients with this severe condition. Unfortunately, its mortality is still high (around 30%) despite therapy. However relapse is uncommon.
Therapeutic advances in musculoskeletal disease, 2015
The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than thr... more The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than three organs or systems developing over a short period of time. Despite conventional treatment with a combination of anticoagulation plus corticosteroids plus plasma exchange, and/or intravenous immunoglobulin, mortality remains high and some patients suffer from recurrent CAPS episodes. In selected patients, new therapies such as rituximab may be a treatment option. In this review, the rationale for using rituximab in CAPS is discussed.
Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregn... more Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregnancy. Moreover, the relationship between SLE and pregnancy is in both directions. However, in the recent years there has been a great change in the perception of the effects of pregnancy on SLE flares and of SLE on pregnancy outcome (both fetal and maternal). The current experience indicates
We performed a meta-analysis to determine whether aspirin has a significant protective effect on ... more We performed a meta-analysis to determine whether aspirin has a significant protective effect on risk of first thrombosis among patients with antiphospholipid antibodies (aPL+). Observational and interventional studies identified from the Medline, Embase and Cochrane databases were selected if they assessed the incidence of first thrombosis in aPL+ patients treated with aspirin versus those without. Pooled effect estimates were obtained using a random-effects model. Of 1211 citation retrieved, 11 primary studies (10 observational and 1 interventional) met inclusion criteria, including a total of 1208 patients and 139 thrombotic events. The pooled odds ratio (OR) for the risk of first thrombosis in patients treated with aspirin (n=601) was 0.50 (95%CI: 0.27 to 0.93) compared to those without aspirin (n=607), with significant heterogeneity across studies (I(2)=46%, p=0.05). Subgroup analysis showed a protective effect of aspirin against arterial (OR: 0.48 [95%CI: 0.28-0.82]) but not venous (OR: 0.58 [95% CI: 0.32-1.06]) thrombosis, as well as in retrospective (OR: 0.23 [0.13-0.42]) but not prospective studies (OR: 0.91 [0.52-1.59]). Subgroup analysis according to underlying disease revealed a significant protective effect of aspirin for asymptomatic aPL+ individuals (OR: 0.50 [0.25-0.99]), for systemic lupus erythematosus (SLE) (OR: 0.55 [0.31-0.98]) and obstetrical antiphospholipid syndrome (APS) (OR: 0.25 [0.10-0.62]). This meta-analysis shows that the risk of first thrombotic event is significantly decreased by low dose aspirin among asymptomatic aPL individuals, patients with SLE or obstetrical APS. Importantly, no significant risk reduction was observed when considering only prospective studies or those with the best methodological quality.
To describe brain magnetic resonance imaging (MRI) abnormalities in newly diagnosed neuropsychiat... more To describe brain magnetic resonance imaging (MRI) abnormalities in newly diagnosed neuropsychiatric lupus (NPSLE). To correlate them with clinical and laboratory data. This retrospective cross-sectional study included patients presenting NPSLE undergoing brain MRI within 6months after onset between 2003 and 2012. Clinical and laboratory data were recorded. MRI findings were defined as inflammatory-like, large-vessel disease (LVD), and small-vessel disease (SVD); SVD was classified as white-matter hyperintensities (WMH), recent small subcortical infarcts, lacunes, microbleeds, and brain atrophy. We included 108 patients (mean 40.6±14.2years; range 14-77), 91.7% women. The most frequent syndromes were headache (28.5%), cerebrovascular disease (15.5%), seizure (15.5%), and cognitive dysfunction (11.4%). Brain abnormalities were found in 59.3%. SVD was the most common (55.6%), followed by LVD (13%) and inflammatory-like lesions (6.5%). The most frequent SVD findings were WMH (53.7%), a...
To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a c... more To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS). The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported. 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment an...
End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with ... more End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Re...
Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (... more Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0±13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus an...
The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by m... more The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastrophic APS is not completely understood. The mortality rate was ~50% in the earliest published series, but recently it has clearly fallen by some 20% due to the use, as first-line therapies, of full anticoagulation, corticosteroids, plasma exchanges, and intravenous immunoglobulins. Cerebral involvement has been identified as the main cause of death, being present in one third of patients, and consisting mainly of stroke, cerebral hemorrhage and encephalopathy, followed by cardiac involvement and infection. The only identified prognostic factor for a higher mortality rate is the presence of systemic lupus erythematosus.
Antiphospholipid syndrome (Hughes syndrome) is characterized by the presence of arterial or venou... more Antiphospholipid syndrome (Hughes syndrome) is characterized by the presence of arterial or venous thrombosis or recurrent miscarriages in a patient with positive laboratory tests for antiphospholipid antibodies (anticardiolipin antibodies and/or lupus anticoagulant and/or anti-beta(2) glycoprotein I). Despite the strong association between antiphospholipid antibodies, and thrombosis and obstetric morbidity, their pathogenic role in the development of these clinical features has not been fully elucidated. At present, patients with thrombosis are treated with long-term oral anticoagulation as standard. The approach for women with obstetric manifestations is based on the use of aspirin plus heparin. However, the knowledge of new pathogenic mechanisms might identify novel therapeutic targets and, therefore, may improve the management of these patients.
To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and ... more To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outc...
The catastrophic variant of the antiphospholipid syndrome (APS) is the most severe and acute form... more The catastrophic variant of the antiphospholipid syndrome (APS) is the most severe and acute form of APS with multiorgan involvement. Patients with this condition have the following features in common: a) clinical evidence of multiple organ involvement developed over a very short time period; b) histopathological evidence of multiple small vessel occlusions, and c) laboratory confirmation of the presence of antiphospholipid antibodies, usually in high titer. The two key pathobiologic mechanisms that cause the clinical manifestations of catastrophic APS are the development of thrombosis and the systemic inflammatory response syndrome. A precipitating factor is reported in more than half of patients. A combination of anticoagulants, corticosteroids, intravenous immunoglobulins and/or plasma exchanges are the treatment modalities advocated for all patients with this severe condition. Unfortunately, its mortality is still high (around 30%) despite therapy. However relapse is uncommon.
Therapeutic advances in musculoskeletal disease, 2015
The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than thr... more The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than three organs or systems developing over a short period of time. Despite conventional treatment with a combination of anticoagulation plus corticosteroids plus plasma exchange, and/or intravenous immunoglobulin, mortality remains high and some patients suffer from recurrent CAPS episodes. In selected patients, new therapies such as rituximab may be a treatment option. In this review, the rationale for using rituximab in CAPS is discussed.
Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregn... more Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregnancy. Moreover, the relationship between SLE and pregnancy is in both directions. However, in the recent years there has been a great change in the perception of the effects of pregnancy on SLE flares and of SLE on pregnancy outcome (both fetal and maternal). The current experience indicates
We performed a meta-analysis to determine whether aspirin has a significant protective effect on ... more We performed a meta-analysis to determine whether aspirin has a significant protective effect on risk of first thrombosis among patients with antiphospholipid antibodies (aPL+). Observational and interventional studies identified from the Medline, Embase and Cochrane databases were selected if they assessed the incidence of first thrombosis in aPL+ patients treated with aspirin versus those without. Pooled effect estimates were obtained using a random-effects model. Of 1211 citation retrieved, 11 primary studies (10 observational and 1 interventional) met inclusion criteria, including a total of 1208 patients and 139 thrombotic events. The pooled odds ratio (OR) for the risk of first thrombosis in patients treated with aspirin (n=601) was 0.50 (95%CI: 0.27 to 0.93) compared to those without aspirin (n=607), with significant heterogeneity across studies (I(2)=46%, p=0.05). Subgroup analysis showed a protective effect of aspirin against arterial (OR: 0.48 [95%CI: 0.28-0.82]) but not venous (OR: 0.58 [95% CI: 0.32-1.06]) thrombosis, as well as in retrospective (OR: 0.23 [0.13-0.42]) but not prospective studies (OR: 0.91 [0.52-1.59]). Subgroup analysis according to underlying disease revealed a significant protective effect of aspirin for asymptomatic aPL+ individuals (OR: 0.50 [0.25-0.99]), for systemic lupus erythematosus (SLE) (OR: 0.55 [0.31-0.98]) and obstetrical antiphospholipid syndrome (APS) (OR: 0.25 [0.10-0.62]). This meta-analysis shows that the risk of first thrombotic event is significantly decreased by low dose aspirin among asymptomatic aPL individuals, patients with SLE or obstetrical APS. Importantly, no significant risk reduction was observed when considering only prospective studies or those with the best methodological quality.
To describe brain magnetic resonance imaging (MRI) abnormalities in newly diagnosed neuropsychiat... more To describe brain magnetic resonance imaging (MRI) abnormalities in newly diagnosed neuropsychiatric lupus (NPSLE). To correlate them with clinical and laboratory data. This retrospective cross-sectional study included patients presenting NPSLE undergoing brain MRI within 6months after onset between 2003 and 2012. Clinical and laboratory data were recorded. MRI findings were defined as inflammatory-like, large-vessel disease (LVD), and small-vessel disease (SVD); SVD was classified as white-matter hyperintensities (WMH), recent small subcortical infarcts, lacunes, microbleeds, and brain atrophy. We included 108 patients (mean 40.6±14.2years; range 14-77), 91.7% women. The most frequent syndromes were headache (28.5%), cerebrovascular disease (15.5%), seizure (15.5%), and cognitive dysfunction (11.4%). Brain abnormalities were found in 59.3%. SVD was the most common (55.6%), followed by LVD (13%) and inflammatory-like lesions (6.5%). The most frequent SVD findings were WMH (53.7%), a...
To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a c... more To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS). The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported. 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment an...
End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with ... more End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Re...
Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (... more Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0±13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus an...
The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by m... more The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastrophic APS is not completely understood. The mortality rate was ~50% in the earliest published series, but recently it has clearly fallen by some 20% due to the use, as first-line therapies, of full anticoagulation, corticosteroids, plasma exchanges, and intravenous immunoglobulins. Cerebral involvement has been identified as the main cause of death, being present in one third of patients, and consisting mainly of stroke, cerebral hemorrhage and encephalopathy, followed by cardiac involvement and infection. The only identified prognostic factor for a higher mortality rate is the presence of systemic lupus erythematosus.
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